Gene
Entrez ID Entrez Gene ID - the GENE ID in NCBI Gene database.
9448
Gene name Gene Name - the full gene name approved by the HGNC.
Mitogen-activated protein kinase kinase kinase kinase 4
Gene symbol Gene Symbol - the official gene symbol approved by the HGNC.
MAP4K4
Synonyms (NCBI Gene) Gene synonyms aliases
FLH21957, HEL-S-31, HGK, MEKKK4, NIK
Chromosome Chromosome number
2
Chromosome location Chromosomal Location - indicates the cytogenetic location of the gene or region on the chromosome.
2q11.2
Summary Summary of gene provided in NCBI Entrez Gene.
The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of
SNPs SNP information provided by dbSNP.
SNP ID Visualize variation Clinical significance Consequence
rs781410462 G>A Likely-pathogenic Coding sequence variant, missense variant
miRNA miRNA information provided by mirtarbase database.
miRTarBase ID miRNA Experiments Reference
MIRT052966 hsa-miR-520e Luciferase reporter assay, qRT-PCR, Western blot 22105365
MIRT053693 hsa-miR-181a-5p Microarray 22942087
MIRT053751 hsa-miR-31-5p Immunoblot, Immunohistochemistry, Luciferase reporter assay, qRT-PCR 22948084
MIRT437487 hsa-miR-141-3p PANC-1 24013097
MIRT735663 hsa-miR-582-3p Immunohistochemistry (IHC) 33510968
Gene ontology (GO) Gene ontology information of associated ontologies with gene provided by GO database.
GO ID Ontology Definition Evidence Reference
GO:0000165 Process MAPK cascade IBA
GO:0000166 Function Nucleotide binding IEA
GO:0001953 Process Negative regulation of cell-matrix adhesion NAS 25490267
GO:0004111 Function Creatine kinase activity IDA 23207904
GO:0004672 Function Protein kinase activity IEA
Other IDs Other ids provides unique ids of gene in databases such as OMIM, HGNC, ENSEMBLE.
MIM HGNC e!Ensembl
604666 6866 ENSG00000071054
Protein
UniProt ID O95819
Protein name Mitogen-activated protein kinase kinase kinase kinase 4 (EC 2.7.11.1) (HPK/GCK-like kinase HGK) (MAPK/ERK kinase kinase kinase 4) (MEK kinase kinase 4) (MEKKK 4) (Nck-interacting kinase)
Protein function Serine/threonine kinase that plays a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway (PubMed:9890973). Activator of the Hippo signaling pathway which plays a piv
PDB 4OBO , 4OBP , 4OBQ , 4RVT , 4U3Y , 4U3Z , 4U40 , 4U41 , 4U42 , 4U43 , 4U44 , 4U45 , 4ZK5 , 4ZP5 , 5DI1 , 5J95 , 5W5Q , 8V5I
Family and domains

Pfam

Accession ID Position in sequence Description Type
PF00069 Pkinase 25 289 Protein kinase domain Domain
PF00780 CNH 930 1210 CNH domain Family
Tissue specificity TISSUE SPECIFICITY: Widely expressed. Isoform 5 is abundant in the brain. Isoform 4 is predominant in the liver, skeletal muscle and placenta. {ECO:0000269|PubMed:9890973}.
Sequence
MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTE
DEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSPPGHDDQLWLVMEFCGAGSITDLVKNT
KGNTLKEDWIAYISREILRGLAHLHIHHVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR
TVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWSCGITAIEMAEGAPPLCDMHPMR
ALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQRPSTEQLLKHPFI
RDQPNERQVRI
QLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVPEQEGEPSSIVNVPGESTLRRDFLRLQ
QENKERSEALRRQQLLQEQQLREQEEYKRQLLAERQKRIEQQKEQRRRLEEQQRREREAR
RQQEREQRRREQEEKRRLEELERRRKEEEERRRAEEEKRRVEREQEYIRRQLEEEQRHLE
VLQQQLLQEQAMLLECRWREMEEHRQAERLQRQLQQEQAYLLSLQHDHRRPHPQHSQQPP
PPQQERSKPSFHAPEPKAHYEPADRAREVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRS
ESFSNGNSESVHPALQRPAEPQVPVRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSIE
PRLLWERVEKLVPRPGSGSSSGSSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRL
ENAVKKPEDKKEVFRPLKPADLTALAKELRAVEDVRPPHKVTDYSSSSEESGTTDEEDDD
VEQEGADESTSGPEDTRAASSLNLSNGETESVKTMIVHDDVESEPAMTPSKEGTLIVRQT
QSASSTLQKHKSSSSFTPFIDPRLLQISPSSGTTVTSVVGFSCDGMRPEAIRQDPTRKGS
VVNVNPTNTRPQSDTPEIRKYKKRFNSEILCAALWGVNLLVGTESGLMLLDRSGQGKVYP
LINRRRFQQMDVLEGLNVLVTISGKKDKLRVYYLSWLRNKILHNDPEVEKKQGWTTVGDL
EGCVHYKVVKYERIKFLVIALKSSVEVYAWAPKPYHKFMAFKSFGELVHKPLLVDLTVEE
GQRLKVIYGSCAGFHAVDVDSGSVYDIYLPTHIQCSIKPHAIIILPNTDGMELLVCYEDE
GVYVNTYGRITKDVVLQWGEMPTSVAYIRSNQTMGWGEKAIEIRSVETGHLDGVFMHKRA
QRLKFLCERN
DKVFFASVRSGGSSQVYFMTLGRTSLLSW
Sequence length 1239
Interactions View interactions
Pathways Pathway information has different metabolic/signaling pathways associated with genes.
  KEGG   Reactome
  MAPK signaling pathway   Oxidative Stress Induced Senescence
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Associated diseases Disease associations categorized as Causal (pathogenic variants), Unknown (uncertain genetic evidence), or Text Mining (literature-based associations)
Causal Diseases caused by PATHOGENIC or LIKELY PATHOGENIC variants from ClinVar only
Disease merge term Disease name dbSNP ID References
cerebral arteriovenous malformation Cerebral arteriovenous malformation rs781410462 N/A
Unknown Includes: (1) ClinVar NON-pathogenic variants (Uncertain, Benign, Conflicting, VUS), (2) GenCC associations, (3) GWAS associations, (4) CBGDA evidence-based associations. NOTE: Diseases with pathogenic evidence are excluded to avoid conflicts.
Disease merge term Disease name Evidence References Source
Alzheimer disease Alzheimer's disease or family history of Alzheimer's disease N/A N/A GWAS
Asthma Asthma (time to onset), Asthma, Asthma (childhood onset), Atopic asthma, Asthma (adult onset) N/A N/A GWAS
Glioblastoma Glioblastoma Inhibiting MAP4K4 blocks migration of four adult glioblastoma cell lines 31570734 CBGDA
Inflammatory Bowel Disease Inflammatory bowel disease N/A N/A GWAS
Associations from Text Mining Disease associations identified through Pubtator
Disease Name Relationship Type References
Autism Spectrum Disorder Associate 36469137
Azoospermia Inhibit 36497065
Bantu siderosis Associate 18840782
Breast Neoplasms Associate 25148458, 37312710
Carcinogenesis Associate 26269113
Carcinoma Hepatocellular Associate 20857524
Cardiomyopathies Associate 32694738
Cardiotoxicity Associate 32694738
Colorectal Neoplasms Associate 26499327, 29138007, 30361904
Developmental Disabilities Associate 36469137